Related Experiment Video
Updated: Jun 3, 2026
08:05
Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
GST pi modulates JNK activity through a direct interaction with JNK substrate, ATF2
Anastasia F Thévenin1, Chati L Zony, Brian J Bahnson
1Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
Protein Science : a Publication of the Protein Society
|March 9, 2011
Summary
Glutathione S-transferase pi (GSTpi) inhibits JNK enzymes, crucial for cell signaling, by interacting with their substrate ATF2. This interaction, particularly with active JNK1, impacts cell proliferation and tumor growth.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- Human glutathione S-transferase pi (GSTpi) is a detoxification enzyme implicated in modulating c-Jun N-terminal kinases (JNKs).
- GSTpi's role in inhibiting apoptosis and promoting cell proliferation suggests a link to tumor growth.
- Previous studies proposed GSTpi as a JNK substrate, requiring further investigation.
Purpose of the Study:
- To analyze the in vitro interaction between GSTpi and JNK isoforms (active and inactive).
- To elucidate the mechanism by which GSTpi inhibits JNK activity.
- To characterize the direct interaction between GSTpi and its substrate ATF2.
Main Methods:
- In vitro enzyme assays to measure JNK activity.
- Binding studies using GSTpi and JNK isoforms (JNK1, JNK2).
- Analysis of GSTpi-ATF2 interactions under various conditions.
Main Results:
- Two GSTpi haplotypes (A and C) inhibited active JNK1/JNK2 phosphorylation of ATF2, with Haplotype C being more potent.
- GSTpi does not act as a JNK substrate.
- GSTpi preferentially binds to active, phosphorylated JNK1 and also directly interacts with ATF2.
Conclusions:
- GSTpi inhibits JNK activity through a mechanism involving competition for the substrate ATF2.
- The interaction is isoform-specific for active JNKs and involves direct binding to ATF2.
- Understanding this GSTpi-JNK-ATF2 interaction is crucial for insights into cell proliferation and tumor development.
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
01:25cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...